Diglycolic acid inhibits succinate dehydrogenase activity, depletes mitochondrial membrane potential, and induces inflammation in an SH-SY5Y neuroblastoma model of neurotoxicity in vitro
Reed, K.J. and Landry, G.M. (2023) Diglycolic acid inhibits succinate dehydrogenase activity, depletes mitochondrial membrane potential, and induces inflammation in an SH-SY5Y neuroblastoma model of neurotoxicity in vitro.Toxicol. Appl. Pharmacol.463, 116414. DOI:10.1016/j.taap.2023.116414
二甘醇(度)是一种广泛使用的有毒的溶胶vent that causes hepatotoxicity, nephrotoxicity and neurological symptoms. Diglycolic acid (DGA) is the final metabolite of DEG that has been identified as the cause of liver and kidney toxicity in vitro. Recent studies suggest that DGA may also be responsible for the neurotoxicity observed with DEG poisoning.
SH-SY5Y neuroblastoma cells are a well-studied cell model for neurotoxicity. Calcium levels affect neuronal cell health, so this study added various amounts of DGA to intact cells and measured calcium levels. Intracellular calcium levels decreased over time, indicating that DGA chelated cellular calcium. Another measure of acute neurotoxicity is altering mitochondrial membrane potential. In SH-SY5Y cells, increasing concentrations of DGA disrupted mitochondrial membrane potential. DGA is known to induce apoptosis, and ATP levels are a measure of cell health. This study also examined the ATP levels in SH-SY5Y cells exposed to DGA over time. The highest concentration of DGA saw a significant drop in cellular ATP at 24 and 48 hours. The highest concentration of DGA also induced inflammation in the neuronal SH-SY5Y cells as measured by the release of IL-1β and TNF-α after 24 and 48 hours. Thus, the study shows in the neurotoxicity model SH-SY5Y cells that DGA is likely responsible for the toxic brain effects of DEG poisoning.
Keywords:succinate dehydrogenase, TNF-alpha, IL-1beta, diglycolic acid, diethylene glycol poisoning
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